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Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference

September 22, 2010 / Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , ,

Abstract

Modulating glutamatergic neurotransmission induces alterations in conscious experience that mimic the symptoms of early psychotic illness. We review studies that use intravenous administration of ketamine, focusing on interindividual variability in the profundity of the ketamine experience. We will consider this individual variability within a hypothetical model of brain and cognitive function centered upon learning and inference. Within this model, the brains, neural systems, and even single neurons specify expectations about their inputs and responding to violations of those expectations with new learning that renders future inputs more predictable. We argue that ketamine temporarily deranges this ability by perturbing both the ways in which prior expectations are specified and the ways in which expectancy violations are signaled. We suggest that the former effect is predominantly mediated by NMDA blockade and the latter by augmented and inappropriate feedforward glutamatergic signaling. We suggest that the observed interindividual variability emerges from individual differences in neural circuits that normally underpin the learning and inference processes described. The exact source for that variability is uncertain, although it is likely to arise not only from genetic variation but also from subjects’ previous experiences and prior learning. Furthermore, we argue that chronic, unlike acute, NMDA blockade alters the specification of expectancies more profoundly and permanently. Scrutinizing individual differences in the effects of acute and chronic ketamine administration in the context of the Bayesian brain model may generate new insights about the symptoms of psychosis; their underlying cognitive processes and neurocircuitry.

Corlett, P. R., Honey, G. D., Krystal, J. H., & Fletcher, P. C. (2011). Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference. Neuropsychopharmacology Reviews, 36, 294–315. http://dx.doi.org/10.1038/npp.2010.163
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Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire

September 21, 2010 / LSD, Neuroscience, Papers, Publications / By / , , , ,

Abstract

Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder and related visual abnormalities in hallucinogen users. We used an online questionnaire to document the symptoms and relationship to drug use of unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet and 2679 were included in the study. Of these, 224 reported having unrelated diagnoses associated with unusual visual experiences and were excluded from main analyses. Most (60.6%) of the remaining 2455 participants reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 4.2% of the sample) found them distressing or impairing enough to consider seeking treatment. Visual changes in hallucinogen users may be more common than previously suspected and are worthy of further study.

Baggott, M. J., Coyle, J. R., Erowid, E., Erowid, F., & Robertson, L. C. (2011). Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire. Drug and alcohol dependence, 114(1), 61-67. http://dx.doi.org/10.1016/j.drugalcdep.2010.09.006
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Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

September 20, 2010 / Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications / By / , , ,

Abstract

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and longterm subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1–4 oral doses of psilocybin (45–315mg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Studerus, E., Kometer, M., Hasler, F., & Vollenweider, F. X. (2010). Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. Journal of Psychopharmacology, 25(11), 1434-1452. http://dx.doi.org/10.1177/0269881110382466
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Nature smokkelt psychedelica de blogosfeer binnen

December 2, 2021 / Uncategorized / By

blogo508

In het kader van het recent gepubliceerde artikel The neurobiology of psychedelic drugs: implications for the treatment of mood disorders heeft wetenschappelijk tijdschrift Nature vier bekende neuroscience bloggers benaderd om elk een ander aspect van de geneeskundige toepassingen van psychedelica onder de loep te nemen, en dit toegankelijk te maken voor een breed publiek.

Neuroskeptic beschrijft de invloed van LSD, Psilocybine en Mescaline op het serotonerge systeem en hoe dit tot een behandeling van depressie zou kunnen leiden.

The Neurocritic vraagt zich af of Ketamine wellicht zou helpen tegen deze zelfde aandoening.

Vaughan Bell beschouwt voor Mind Hacks de therapeutische mogelijkheden van DMT.

En tot slot schrijft Moheb Costandi voor Neurophilosophy over het vroegere gebruik van LSD in de psychiatrie. Bovendien vatte hij de vier posts samen in een artikel voor de Britse krant The Guardian.

Nature brings psychedelics to the blogosphere

December 6, 2021 / Publications / By

blogo508

In the context of the recent paper The neurobiology of psychedelic drugs: implications for the treatment of mood disorders scientific journal Nature has approached four well-known neuroscience bloggers to each blog about a different aspect of the medical applications of psychedelic drugs.

Neuroskeptic describes how LSD, Psilocybin and Mescaline affect the serotonergic system and considers a psychedelic treatment for depression.

The Neurocritic wonders whether Ketamine might be able to treat this same disorder.

Vaughan Bell over at Mind Hacks covers the therapeutic potential of DMT.

Moheb Costandi from Neurophilosophy investigates the “secret history of psychedelic psychiatry.” On top of that he wrote an overview discussing all four posts for British newspaper The Guardian.

The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

September 10, 2010 / Depressive Disorders, DMT, Ketamine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

Vollenweider, F. X., & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, 11, 642-651. http://dx.doi.org/10.1038/nrn2884
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Intrahippocampal LSD accelerates learning and desensitizes the 5-HT2A receptor in the rabbit

September 9, 2010 / LSD, Papers, Publications / By / , , , , , ,

Abstract

Rationale: Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT2A receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT2A-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning.

Objective: This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT2A-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning.

Materials and methods: LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT2A receptor as measured by a decrease in DOI-elicited head bobs.

Results: Acute parenteral or intrahippocampal LSD elicited a 5-HT2A but not a 5-HT2C-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls.

Conclusions: LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT2A receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT2A receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Romano, A. G., Quinn, J. L., Li, L., Dave, K. D., Schindler, E. A., Aloyo, V. J., & Harvey, J. A. (2010). Intrahippocampal LSD accelerates learning and desensitizes the 5-HT2A receptor in the rabbit. Psychopharmacology, 212(3), 441–448. http://dx.doi.org/10.1007/s00213-010-2004-7
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DEA geeft goedkeuring voor MDMA/PTSD-studie

December 2, 2021 / Uncategorized / By

Wederom nieuws op het onderzoek-vlak: op 27 augustus 2010 heeft de DEA, een Amerikaanse overheidsorganisatie die gaat over de wetten met betrekking tot ‘controlled substances’ in Amerika, zijn goedkeuring gegeven voor een onderzoek naar de effecten van MDMA bij oorlogsveteranen met een posttraumatische stressstoornis. MAPS kan nu aan de slag met het onderzoek, dat $500.000 kost en ongeveer twee jaar in beslag zal nemen. Het grootste deel van het budget moet nog bij elkaar gevonden worden, maar het is zeker een stap in de goede richting!

Op de conferentie van OPEN (23-24 oktober 2010) kun je meer horen over dit soort onderzoeken. Kijk hier voor meer informatie.

DEA approves MDMA/PTSD study

December 6, 2021 / MDMA, Publications / By

More news on the subject of research: on august 27th 2010 the DEA, an American government organisation in charge of the laws regarding ‘controlled substances’ in the US, has approved a study regarding the effects of MDMA on war veterans suffering from post-traumatic stress syndrome. MAPS can go ahead with the research, which will cost $500,000 and will take the good part of two years. Most of the budget still has to be found, but it’s a step in the right direction!

On the OPEN conference (october 23/24) you can hear more about these kinds of studies. Click here for more information.

Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users

September 1, 2010 / Ayahuasca, DMT, Papers, Psychology, Publications / By / ,

Abstract

Dimethyltryptamine (DMT) is an endogenous hallucinogen with traditional use as a sacrament in the orally active preparation of ayahuasca. Although the religious use of ayahuasca has been examined extensively, very little is known about the recreational use of DMT. In this study, Australian participants (n = 121) reporting at least one lifetime use of DMT completed an online questionnaire recording patterns of use, subjective effects and attitudes towards their DMT use. Smoking DMT was by far the most common route of administration (98.3%) with a comparatively smaller proportion reporting use of ayahuasca (30.6%). The reasons for first trying DMT were out of a general interest in hallucinogenic drugs (46.6%) or curiosity about DMT’s effects (41.7%), while almost one-third (31.1%) cited possible psychotherapeutic benefits of the drug. An increase in psychospiritual insight was the most commonly reported positive effect of both smoked DMT (75.5%) and ayahuasca (46.7%), a finding that is consistent with other studies examining the ritualised use of ayahuasca in a religious context. Although previous studies of DMT use have examined ayahuasca use exclusively, the present study demonstrates the ubiquity of smoking as the most prevalent route of administration among recreational DMT users.

Cakica, V., Potkonyakb, J., & Marshalla, A. (2010). Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users. Drug and Alcohol Dependence, 111(1-2), 30-37. http://dx.doi.org/10.1016/j.drugalcdep.2010.03.015
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